Drug delivery compositions and medical devices containing block copolymer

Abstract

A composition for delivery of a therapeutic agent is provided. The composition comprises: (a) a biocompatible block copolymer comprising one or more elastomeric blocks and one or more thermoplastic blocks and (b) a therapeutic agent, wherein the block copolymer is loaded with the therapeutic agent. The block copolymer is preferably of the formula X-(AB) n , where A is an elastomeric block, B is a thermoplastic block, n is a positive whole number and X is a seed molecule. The elastomeric blocks are preferably polyolefin blocks, and the thermoplastic blocks are preferably selected from vinyl aromatic blocks and methacrylate blocks. According to another aspect of the invention, a medical device is provided, at least a portion of which is insertable or implantable into the body of a patient. The medical device comprises (a) the above biocompatible block copolymer and (b) a therapeutic agent, wherein the block copolymer is loaded with the therapeutic agent. According to another aspect of the present invention, a method of treatment is provided in which the above device is implanted or inserted into a patient, resulting in the release of therapeutic agent in the patient over an extended period. According to yet another aspect of the invention, a coated medical device is provided which comprises: (a) an intravascular or intervascular medical device and (b) a coating over at least a portion of the intravascular or intervascular a medical device, wherein the coating comprises the above biocompatible block copolymer.

1. A medical device which is insertable or implantable into the body of a patient, comprising:
 a block copolymer comprising one or more elastomeric blocks and one or more thermoplastic blocks, wherein the elastomer blocks are polyolefin blocks and the amount of polyolefin blocks ranges from between 95 and 45 mol % of the block copolymer; and 
 a therapeutic agent, said block copolymer being loaded with said therapeutic agent, wherein the entirety of the medical device is formed from the block copolymer loaded with said therapeutic agent. 
 
     
     
       2. The medical device of  claim 1 , wherein said one or more thermoplastic blocks are vinyl aromatic blocks or methacrylate blocks. 
     
     
       3. The medical device of  claim 1 , wherein said block copolymer is of the formula X-(AB) n , where A is an elastomeric block, B is a thermoplastic block, n is a positive whole number and X is a seed molecule. 
     
     
       4. The medical device of  claim 3 , wherein B is a vinyl aromatic block or methacrylate polymer block. 
     
     
       5. The medical device of  claim 4 , wherein A is a polyolefin block of the general formula —(CRR′—CH 2 ) n —, where R and R′ are linear or branched aliphatic groups or cyclic aliphatic groups and wherein B is a vinyl aromatic polymer block. 
     
     
       6. The medical device of  claim 5 , wherein said polyolefin block comprises an isobutylene monomer and wherein said vinyl aromatic polymer block comprises one or more monomers selected from polystyrene and poly-α-methylstyrene. 
     
     
       7. The medical device of  claim 2 , wherein therapeutic agent is adapted for releasing the therapeutic agent over an extended period after implantation in a patient. 
     
     
       8. The medical device of  claim 2 , wherein the medical device is adapted such that at least a portion of said block copolymer is exposed to bodily fluid upon insertion or implantation in the body. 
     
     
       9. The medical device of  claim 2 , wherein the medical device is adapted such that at least a portion of said block copolymer is exposed to tissue upon insertion or implantation in the body. 
     
     
       10. The medical device of  claim 2 , wherein said medical device is a catheter, guide wire, balloon, filter, stent, stent graft, vascular graft, vascular patch, shunt or intraluminal paving system. 
     
     
       11. The medical device of  claim 2 , wherein said medical device is adapted for implantation or insertion into the coronary vasculature, peripheral vascular system, esophagus, trachea, colon, biliary tract, urinary tract, prostate or brain. 
     
     
       12. The medical device of  claim 2 , wherein said medical device is a stent or catheter which further comprises a sheath for covering the block copolymer during insertion into the body to prevent premature therapeutic agent release. 
     
     
       13. The medical device of  claim 2 , wherein said therapeutic agent is selected from one or more of the group consisting of an anti-thrombotic agent, an anti-proliferative agent, an anti-inflammatory agent, an anti-migratory agent, an agent affecting extracellular matrix production and organization, an antineoplastic agent, an anti-mitotic agent, an anesthetic agent, an anti-coagulant, a vascular cell growth promotor, a vascular cell growth inhibitor, a cholesterol-lowering agent, a vasodilating agent, and an agent that interferes with endogenous vasoactive mechanisms. 
     
     
       14. The medical device of  claim 2 , wherein said therapeutic agent is selected from anti-sense DNA, anti-sense RNA, DNA coding for anti-sense RNA, DNA coding for tRNA or rRNA, DNA coding for angiogenic factors, DNA coding for cell cycle inhibitors, DNA coding for cell proliferation inhibition agents, and DNA coding for bone morphogenic proteins. 
     
     
       15. The medical device of  claim 2 , wherein said therapeutic agent is selected from autologous cells, allogeneic cells and xenogeneic cells. 
     
     
       16. The medical device of  claim 1 , further comprising a polymer or copolymer selected from the group consisting of a polycarboxylic acid, a cellulose acetate polymer, a cellulose nitrate polymer, a gelatin, a polyvinylpyrrolidone, a cross-linked polyvinylpyrrolidone, a polyanhydride, a polyamide, a polyvinyl alcohol, a polyvinyl ether, a polyvinyl aromatic, a polyethylene oxide, a glycosaminoglycan, a polysaccharide, a polyester, a polyacrylamide, a polyether, a polyether sulfone, a polycarbonate, a polyalkylene, a halogenated polyalkylene, a polyurethane, a polyorthoester, a polypeptide, a silicone, a siloxane polymer, a polylactic acid, a polyglycolic acid, a polycaprolactone, a polyhydroxybutyrate valerate, a fibrin, a collagen, a collagen derivative, a hyaluronic acid and combinations of any of the foregoing. 
     
     
       17. The medical device of  claim 16 , wherein said polymer or copolymer is selected from a polyacrylic acid, an ethylene-vinyl acetate copolymer, and a copolymer of polylactic acid and polycaprolactone. 
     
     
       18. The medical device of  claim 16 , wherein said polymer or copolymer is blended with said biocompatible block copolymer. 
     
     
       19. The medical device of  claim 16 , wherein said polymer or copolymer is provided in a layer that does not contain said biocompatible block copolymer. 
     
     
       20. The medical device of  claim 1  wherein:
 (a) the elastomeric blocks are selected from the group consisting of polyolefin blocks of the formula —(CRR′—CH 2 ) n —, where R and R′ are linear or branched aliphatic groups or cyclic aliphatic groups and n is selected to give a molecular weight in the range of 60,000-200,000 Daltons; and 
 (b) the thermoplastic blocks are selected from the group consisting of vinyl aromatic blocks and methacrylate blocks having a molecular weight in the range of 20,000-100,000 Daltons. 
 
     
     
       21. The medical device of  claim 16  wherein the additional polymer or copolymer can either be (a) blended with the block copolymer or (b) provided in a layer that does not contain the block copolymer.